Macromolecular agents composed of serum albumins or linear polymers have MRI contrast enhancement factors less than those predicted for rigid molecules of comparable size. To obviate this deficiency, MRI contrast agents developed based upon dendrimers, wherein terminal primary amines are modified with chelating agents that subsequently form Gd(III) complexes. These reagents possess a molar relaxivity up to 6 times that of simple Gd-DTPA, currently employed in the clinic, and better than twice that of other macromolecular agents. Excellent conventional MR imaging and 3D T-O-F MR angiograms have been obtained and studies have been expanded to thoroughly explore the utility of these agents. Ongoing experiments in a canine model system have already demonstrated outstanding detailed imaging of the vasculature and potential development as blood pool agents when using the G6 generation dendrimer construct. Due to results indicative of vasculature leakage of this particular reagent, the G8 dendrimer analog has demonstrated that this leakage can be reduced to nearly insignificant levels. This reagent, as well as the G6 analog, continues to be evaluated for utility as an MRI contrast agent in both canine and murine systems. The ongoing project to develop ligands for Pb(II) previously had possessed a component whereby ligands derived from calix[4]arenes produced numerous chelating agents that have since been evaluated for forming complexes with Gd(III). One such complex has recently been found to not only for an exceptional Gd(III) complex, but also to form a significant hydrophilic binding interaction with albumin that confered a greatly increased relaxivity that would promote use of this ligand as an MRI vascular imaging reagent. This complex continues to be evaluated and introduction into murine models is curently being planned. A CT contrast agent based upon albumin conjugated to iopanoic is currently being evaluated in pre-clinical models for use in quantitating flow and dispersion of therapeutics being injected inter-cranially. This material is being compared versus a comparable MRI albumin based reagent and preparations are underway to prepare the iodine based reagent for use in clinical trials. Use of dendrimers to prepare a completely synthetic, and hence reproducible analog of the CT albumin reagent has been initiated. Dendrimers of the G4 generation approach the MW of the albumin reagent, yet possess signficantly greater numbers of reactive functional groups by which poly-iodinated CT contrast agents might be conjugated. A water soluble analogo of iopanoic acid has been prepared for this purpose and development of the chemistry necessary to prepare the targeted products is being performed. - imaging, MRI contrast agents, CT contrast agents,
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